The present invention relates to methods and apparatus for analysing embryo development. In particular, some embodiments relate to methods and apparatus for establishing values for a plurality of parameters (variables/indicators) relating to the development of an embryo, for example, timings for certain cell division events.
Infertility affects more than 80 million people worldwide. It is estimated that 10% of all couples experience primary or secondary infertility. In vitro fertilization (IVF) is an elective medical treatment that may provide a couple who has been otherwise unable to conceive a chance to establish a pregnancy. It is a process in which eggs (oocytes) are taken from a woman's ovaries and then fertilized with sperm in the laboratory. The embryos created in this process are then placed into the uterus for potential implantation. In between fertilization (insemination) and transfer the embryos are typically stored in an incubation chamber of an incubator for 2-6 days during which time they may be regularly monitored, for example through imaging, to assess their development. Conditions within the incubator, such as temperature and atmospheric composition, are controlled, generally with a view to emulating the conditions in the oviduct and uterus.
In a typical IVF cycle a number of eggs from a single patient will be fertilized and the resulting embryos incubated. However, it is usual for not all incubated embryos to be transferred to the patient's uterus. This is to reduce the risk of potentially dangerous multiple births. Embryos will typically be selected for transfer on the basis of an assessment of the development potential of the embryos that have been incubated. Embryos determined to have the greatest potential for developing into a live birth will be preferentially selected over other embryos in their cohort. Accordingly, an important aspect of IVF treatment is assessing development potential of the embryos comprising a cohort, i.e. determining embryo quality where embryo quality is a prediction representing the likelihood of an embryo successfully implanting, developing in the uterus after transfer and leading to the birth of a healthy baby.
A powerful tool for assessing embryo quality that has recently been developed is time-lapse embryo imaging. Time-lapse embryo imaging involves obtaining images of embryos during their development. This can allow the timings of various developmental events, such as cell divisions, to be established. These timings may sometimes be referred to as morphokinetic parameters for the embryo. Studies have shown how the timings and durations of various embryonic development events can be correlated with development potential for an embryo. For example, a relatively early time of division from one cell to two cells has been found to be an indicator of a good quality embryo. Other morphokinetic parameters, for example the degree of synchronicity in the two divisions when dividing from two cells to four cells, are also found to be sensitive to embryo quality. More generally, there has been proposed various approaches for assessing the development potential of an embryo from parameters relating to the embryo's in-vitro development. Consequently it can be important when assessing embryo quality using time-lapse imaging to establish values for various parameters relating to the timings of various embryo development events and/or other characteristics relating to the development of the embryo, for example in terms of cell-uniformity (evenness) at different stages, the appearance of pro-nuclei (PN), and the presence of multi-nucleation (MN). To establish values for parameters relating to embryo development from a series of time-lapse images a user will typically view the series of time-lapse images as a movie to identify the images (and hence timings) associated with events of interest and to identify images in which other characteristics (such as unevenness, PN appearance, and MN) can be assessed. This process of establishing values for parameters of interest from a time-lapse series of images is sometimes called annotation.
One well-known apparatus for performing time-lapse embryo imaging is the EmbryoScope® device and associated EmbryoViewer® software developed by, and available from, Unisense FertiliTech A/S (Aarhus, Denmark).
Annotation is generally performed by skilled embryologists and can take a relatively long time to perform. This is because in addition to making the relevant clinical assessments for the respective parameters of interest, the user needs to navigate through what can be a relatively long series of images, and furthermore will typically do this for a number of different embryos for each patient.
U.S. Pat. No. 7,672,369 B2 [1] discloses an approach in which parameters of interest may be established automatically by comparing simulated images of cell models to observed data. U.S. Pat. No. 7,963,906 B2 [2] also describes schemes for automated image processing of images. While automated methods avoid the need for manual annotation, the corresponding lack of skilled clinical assessment may give cause for concern.
The process of reliably establishing values for parameters of interest relating to the development of embryos from time-lapse images in accordance with current techniques can therefore be a relatively time intensive process. Accordingly there is a desire for schemes which can help a user establish values for a plurality of parameters of interest relating to the development of an embryo from a series of images, for example by helping a user perform the annotations more quickly.